Identification of an intermediate signature that marks the initial phases of colorectal adenoma-carcinoma transition

The colorectal adenoma-carcinoma sequence describes the stepwise progression from normal to dysplastic epithelium and then to carcinoma; only a small proportion of colorectal adenoma (CRA) progresses to colorectal carcinoma (CRC). Presently, endoscopic intervention is used on patients with CRAs of high grade dysplasia, diameters > 1 cm, or villous components > 25% who are at higher risk than other CRA sufferers. During the process, biopsy samples were taken for conventional histological diagnosis, but poor pathomorphological sensitivity and specificity greatly limit the diagnostic accuracy. Unfortunately, there are no reliable molecular criteria available that can predict the potential development of CRA to CRC. In present study, we use microarrays to detail the global programme of gene expression underlying the gradual progress of colorectal adenoma-carcinoma sequence. Gene expression profiles of normal colorectal mucosa (NOR), CRA, and different Duke’s stages of CRC biopsy specimens, which represent the gradual progress of the colorectal adenoma-carcinoma sequence, were determined by Affymetrix technology. Intersectional analysis of discriminative expression signatures of CRC vs. CRA and CRA vs. NOR allowed the identification of the intermediate signature that mark the NOR→CRA→CRC progression. This signature represents a reservoir of candidate markers for early diagnosis of higher-risk CRA during the early stage, allowing timely therapeutic intervention and more selective treatment.